Glycoxidized low-density lipoprotein enhances monocyte chemoattractant protein-1 mRNA expression in human umbilical vein endothelial cells: relation to lysophosphatidylcholine contents and inhibition by nitric oxide donor.
Glycoxidized low-density lipoprotein enhances monocyte chemoattractant protein-1 mRNA expression in human umbilical vein endothelial cells: relation to lysophosphatidylcholine contents and inhibition by nitric oxide donor.
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DOI：
10.1053/meta.2002.34703
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发表时间：
2002-09
期刊：
影响因子：
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通讯作者：
K. Sonoki;M. Yoshinari;M. Iwase;K. Iino;K. Ichikawa;S. Ohdo;S. Higuchi;M. Iida
中科院分区：
文献类型：
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作者：
K. Sonoki;M. Yoshinari;M. Iwase;K. Iino;K. Ichikawa;S. Ohdo;S. Higuchi;M. Iida
糖尿病患者的低密度脂蛋白（LDL）可能比非糖尿病患者经历更多的糖化或氧化。我们研究了糖氧化LDL （goLDL）是否通过激活核因子κ b （NFkappaB）诱导单核细胞趋化蛋白-1 (MCP-1) mRNA的表达，并测定了一氧化氮（NO）对人脐静脉内皮细胞（HUVEC） MCP-1 mRNA表达的影响。氧化（oxLDL）或goLDL可增强HUVEC中MCP-1 mRNA的表达，而与NO供体NOR3预处理可消除这种刺激。goLDL增加了HUVEC中NFkappaB-DNA的结合活性，这种作用也被NOR3抑制。采用电喷雾电离液相色谱/质谱法（LC/MS）测定了改性LDL中溶血磷脂酰胆碱（lyso-PC）的含量，以确定其分子种类。MCP-1 mRNA的表达和NFkappaB的激活与LDL中棕榈酰和硬脂酰-lyso- pc含量显著相关。我们的研究结果表明，糖基化和氧化修饰的LDL可能有助于糖尿病患者动脉粥样硬化的加速发展，这一过程可能通过增加血管NO可用性来预防。
Low-density lipoprotein (LDL) may undergo more glycation or oxidation in patients with diabetes mellitus than in nondiabetic subjects. We investigated whether glycoxidized LDL (goLDL) induces monocyte chemoattractant protein-1 (MCP-1) mRNA expression through activation of nuclear factor-kappaB (NFkappaB), and determined the effect of nitric oxide (NO) on MCP-1 mRNA expression in human umbilical vein endothelial cells (HUVEC). Oxidized (oxLDL) or goLDL enhanced MCP-1 mRNA expression in HUVEC, and preincubation with NOR3, a NO donor, abrogated such stimulation. goLDL increased NFkappaB-DNA binding activity in HUVEC and this effect was also suppressed by NOR3. We measured lysophosphatidylcholine (lyso-PC) contents in modified LDL using electrospray ionization liquid chromatography/mass spectrometry (LC/MS) to identify its molecular species. MCP-1 mRNA expression and NFkappaB activation correlated significantly with palmitoyl- and stearoyl-lyso-PC contents in LDL. Our results suggest that LDL modified by glycation and oxidation may contribute to the development of accelerated atherosclerosis in the presence of diabetes, a process that may be prevented by increased vascular NO availability.